The present invention relates to antimicrobial surface modified silicones and methods of preparation thereof, and more specifically, to silicone catheter materials having antimicrobial and antifouling surface layers.
Intravascular catheters, used mainly to administer fluids, medication, and to monitor hemodynamic status, have become indispensable for medical care in hospitals worldwide. However, these catheters are prone to bacterial adhesion and biofilm formation, which may result in subsequent bloodstream infection. Catheter-associated infections (CAIs) have become one of the most common sources of healthcare-associated infections. In the USA alone, more than 5 million central venous catheters are inserted each year and CAIs have been reported in up to 8% of inserted catheters, resulting in considerable morbidity and mortality. Additional financial costs attributable to CAIs can reach USD30,000 for each episode of infection, along with prolonged hospitalization. Biofilm formation on the catheters is the main cause for the CAIs. Once a mature biofilm is developed, the bacteria growing in the biofilm become highly resistant to both antimicrobial agents and host immune response. Coagulase-negative staphylococci are the most common causes of CAIs, followed by Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA). The latter are more virulent and clinically important, with infections causing greater morbidity and mortality compared to coagulase-negative staphylococci.
Silicone rubber is an extensively used catheter material because of its flexibility, low toxicity and physiological inertness. However, microbes easily adhere to this material and cause infections. Several strategies to modify the silicone rubber surface to overcome this problem have been reported. For example, antibiotics (e.g., rifampin and minocycline) or silver have been coated onto catheter surfaces, and these surface coated catheters do prevent bacterial adhesion and biofilm formation. However, the risk of bacterial resistance and inadequate efficacy have hindered their clinical applications. In other strategies, polyacrylamide brushes and poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) triblock copolymer brushes were grafted onto the silicone rubber surface by polymerization from the silicone rubber surface in multiple steps. These modified silicone rubber surfaces successfully prevented the adhesion of S. aureus, Streptococcus salivarius (S. salivarius), Staphylococcus epidermidis (S. epidermidis) and Candida albicans (C. albicans). However, the complexity of growing polymer brushes from the rubber surface may lead to difficulty in characterization and batch-to-batch variation in coating thickness and quality.
In yet another strategy, thiol-terminated methoxy poly(ethylene glycol) (mPEG-SH) was grafted onto polydopamine coated substrates, and these modified surfaces exhibited antifouling property against mammalian cells for 2 days. Poly(ethylene glycol) (PEG) or PEG-based coatings have been of great interest in the drive to develop antifouling surfaces. However, decreased antifouling performance of PEG coating over time is a major drawback.
Therefore, a pressing need exists to develop a nontoxic, facile and effective catheter coating for the prevention of CAIs on silicone rubber materials.